Project Summary/Abstract The objectives of this community-based participatory research (CBPR) project are to investigate exposures, endocrine effects, and mechanisms of developmental disruption associated with legacy contaminants and emerging flame retardant chemicals in two Yupik communities on St. Lawrence Island (SLI) in arctic Alaska. The Arctic is subject to atmospheric deposition of globally-distilled persistent organic pollutants (POPs), acting as a hemispheric sink for POPs that are transported from lower latitudes. Thus, the Arctic is significant as an indicator region and contains some of the most highly contaminated animals and people in the world. This study addresses a primary public health concern of the people of SLI by focusing on the levels and effects of legacy and emerging contaminants on the development of children in an arctic indigenous population that is vulnerable, underserved, and experiences significant health disparities. Other studies have shown that young children are more highly exposed than adults. Using innovative and minimally invasive techniques, we will assess exposures of children to polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and emerging halogenated and non-halogenated organophosphate flame retardants. We will quantify PCBs and flame retardant chemicals in household dust, known to be an important exposure route. We will assess relationships among contaminant levels and evidence of health disruption via transcriptomics and endocrinology. We will use chemical concentrations in household dust and utilization of a subsistence diet as determined by stable isotope analysis to assess exposure pathways of these compounds. In order to understand the mechanistic basis of developmental disruption, and to have a reference for interpretation of human data, we will monitor patterns of gene expression, endocrinology, and histology of our resident fish model, the stickleback, from both contaminated and reference sites. Collectively, we will increase our understanding of routes of exposure, endocrine disruption, and effects on the transcriptome of Yupik children exposed to high levels of PCBs and flame retardant chemicals. This study provides an opportunity to investigate the levels of PBDEs and emerging flame retardants in nails and blood in relation to health outcomes of arctic indigenous children for the first time. Our CBPR project will also empower SLI communities with the knowledge and tools they need to address important health disparities in their communities. Our results will inform public health interventions and improve health outcomes of arctic children broadly. Furthermore, discovery of bioindicators relevant to early detection of developmental disruption will enable early intervention and improve health outcomes. Importantly, we will build capacity through our CBPR approach, public health interventions, and policy outreach, which will mitigate future exposure of SLI children to toxic chemicals.